Retinoic acid drives hair follicle stem cell activation via Wnt/ß-catenin signalling in androgenetic alopecia.

BACKGROUND: Depletion or permanent quiescence of the hair follicle stem cell (HFSC) pool underlies pathogenesis in androgenetic alopecia (AGA). Reactivation of quiescent HFSCs is considered an efficient treatment strategy for hair loss. The retinoic acid (RA) is critical to ensure stem cell homeostasis and function. However, little is known about whether RA regulates HFSC homeostasis. We aimed to investigate the impact of RA on HFSC homeostasis and the underlying mechanisms, in order to provide new potential targets for medical therapies of AGA. METHODS: Microdissected hair follicles from the occipital and frontal scalp in AGA were obtained for RNA sequencing analysis and test. The C57BL/6 mice model in telogen was established to investigate the effect of exogenous RA. Miniaturized hair follicles from frontal scalp were incubated with or without RA in hair follicle organ culture to test the effects on hair shaft elongation, hair cycling and HFSC activities. A strategy to characterize the effect of RA on HFSC in primary culture was developed to identify novel mechanisms that control HFSC activation. A clinical study was performed to test the efficacy of RA treatment in AGA patients. RESULTS: RA signalling was inhibited in the course of AGA pathogenesis along with HFSC dysfunction. Hair regeneration was retarded in AGA miniaturized hair follicles with RA deficiency, but they tended to recover after treatment with RA. In addition, RA treatment during the telogen phase facilitated HFSC anagen entry and accelerated hair growth. Mechanistically, RA promoted hair growth by stimulating stem cells via Wnt/ß-catenin signalling and accelerating the transition from a dormant to an activated state. Furthermore, a clinical study suggested that RA has obvious advantages in the early intervention of AGA by reactivating HFSCs. CONCLUSIONS: Our study provides insights into the reactivation of HFSCs in AGA and provides potential targets for medical therapies.

Overexpression of miR-122 promotes apoptosis of dermal papilla cells by directly targeting IGF1R in androgenetic alopecia.

Androgenetic alopecia (AGA) is the most common pattern of hair loss resulting from the effects of androgen on hair follicles. MicroRNAs (miRs) serve imperative roles in the regulation of many biological processes of hair follicles. However, the exact molecular mechanism of AGA remains to be elucidated. In the present study, we found miR-122, which is mainly recognized as a tumor suppressor, was highly overexpressed in the bulb of balding hair follicles in comparison with nonbalding ones in AGA. Moreover, miR-122 induces apoptosis of human dermal papilla cells (hDPCs) with miR-122 mimics in vitro, and the expression of insulin-like growth factor 1 receptor (IGF1R) in hDPCs was reduced following upregulation of miR-122. Mechanistically, dual-luciferase reporter assay confirmed that miR-122 directly targeted the 3'-untranslated region of IGF1R. These findings suggested that upregulation of miR-122 induces apoptosis, potentially via the repression of IGF1R in hDPCs of AGA, providing a novel insight into the potential pathological mechanism of miR-122 in AGA DPCs.

Extensive Scarring Alopecia Treated Through a Single Dense-Packing Follicular Unit Extraction Megasession.

BACKGROUND: Follicular unit extraction (FUE) is becoming more popular in hair restoration. However, its potential for treating extensive scarring alopecia is unknown. METHODS: Patients with scarring alopecia larger than 100 cm2 were enrolled from 2015 to 2018. After assessing scar quality regarding vascularity, pliability, and thickness, dense-packing megasession (DPM)-FUE was performed on high-quality recipient sites. Patients were followed up at 1 week and 12 months postoperatively to evaluate complications, survival rates of grafts, and patient satisfactions. Cases of nonscarring alopecia were reviewed as controls. RESULTS: Fifty-two scarring alopecia and 55 nonscarring alopecia patients were enrolled. The mean scar area was 120 cm2, and the procedure required an average of 8 operative hours, with no difference between groups (p > .05). Graft amount and postoperative complications were similar as well (p > .05). The survival rate in scarring alopecia was lower than that in the control but was still 85% (p < .05). Follow-up photographs showed effective scar camouflage after DPM-FUE. Most patients were very satisfied with the final results (p > .05). CONCLUSION: DPM-FUE is a safe and effective treatment for extensive scarring alopecia.

Efficacy of Platelet-Rich Plasma plus Basic Fibroblast Growth Factor on the Treatment of Androgenic Alopecia.

BACKGROUND: Studies have identified platelet-rich plasma (PRP) as a novel adjuvant therapy in androgenetic alopecia (AGA). However, the efficacy of PRP still needs to be improved. The purpose of this study was to assess the efficacy of PRP plus basic fibroblast growth factor (PRPF) for the treatment of AGA. METHODS: This was a prospective randomized, double-blind, placebo-controlled, half-head study. Eighty patients whose AGA was staged Norwood-Hamilton stages III to VII or Ludwig stages I to III were enrolled in the study from February of 2019 to September of 2019. Patients were divided randomly into two groups of 40 patients each and were given the following treatment: group 1, PRPF was injected in the right half and the left half with placebo; group 2, PRPF was injected in the right half and the left half with PRP. The treatment was processed three times, 1 month apart. Hair growth parameters were evaluated by trichoscope monthly until the sixth month of the study. Patient satisfaction, hair pull test, and side effects were recorded during follow-up. RESULTS: Of the 80 patients included in the study, 47 were men and 33 were women with a mean age of 28.96 ± 4.82 years (range, 21 to 46 years). Both PRP and PRPF showed positive improvement ( P < 0.05) on hair count, terminal hair, and anagen hair after the treatment. Efficacy of PRPF revealed a significant improvement ( P < 0.05) in hair count, terminal hair, vellus hair, and anagen hair versus PRP. There was no statistical difference among any of the parameters in the placebo group. CONCLUSION: PRPF can be a safe and valuable form of AGA treatment, and has proven to be more effective than PRP. CLINICAL RELEVANCE STATEMENT: Hybrid therapy of PRP with relative growth factors, such as basic fibroblast growth factor, have prominent efficacy on treatment of AGA. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Dermal macrophage and its potential in inducing hair follicle regeneration.

Hair follicle (HF) is an excellent mini-model to study adult tissue regeneration, since it can regenerate itself under appropriate stress settings via interaction with niche components. Dermal macrophages, a group of heterogeneous cell populations, serve as key regulators in this microenvironment. Recent advances in phenotype identification and lineage tracing have unveiled various dermal macrophage subsets involved in stress-induced hair regeneration through different mechanisms, where HF structural integrity is impaired to varying degrees. This review summarized current knowledge regarding the distribution, sources, phenotypes of dermal macrophages in association with HF, as well as the mechanisms underlying macrophage-mediated hair regeneration in response to different internal-stress settings. Further investigation on macrophage dynamics will provide novel cell-targeting therapies for HF engineering and hair loss.

Emerging Role of Dermal White Adipose Tissue in Modulating Hair Follicle Development During Aging.

Hair follicle stem cells are extensively reprogrammed by the aging process, manifesting as diminished self-renewal and delayed responsiveness to activating cues, orchestrated by both intrinsic microenvironmental and extrinsic macroenvironmental regulators. Dermal white adipose tissue (dWAT) is one of the peripheral tissues directly adjacent to hair follicles (HFs) and acts as a critical macroenvironmental niche of HF. dWAT directly contributes to HF aging by paracrine signal secretion. However, the altered interrelationship between dWAT and HF with aging has not been thoroughly understood. Here, through microdissection, we separated dWAT from the skin of aged mice (18 months) and young mice (2 months) in telogen and depilation-induced anagen for transcriptome comparing. Notably, compared with young dWAT, aberrant inflammatory regulators were recapitulated in aging dWAT in telogen, including substantial overexpressed inflammatory cytokines, matrix metalloproteinases, and prostaglandin members. Nonetheless, with anagen initiation, inflammation programs were mostly abolished in aging dWAT, and instead of which, impaired collagen biosynthesis, angiogenesis, and melanin synthesis were identified. Furthermore, we confirmed the inhibitory effect on hair growth of CXCL1, one of the most significantly upregulated inflammation cytokines in aging dWAT. Besides this, we also identified the under-expressed genes related to Wnt signaling fibroblast growth factor family members and increased BMP signaling in aging dWAT, further unraveling the emerging role of dWAT in aging HFs malfunction. Finally, we proved that relieving inflammation of aging dWAT by injecting high-level veratric acid stimulated HF regenerative behavior in aged mice. Concomitantly, significantly decreased TNF-a, CCL2, IL-5, CSF2, and increased IL10 in dWAT was identified. Overall, the results elaborated on the complex physiological cycling changes of dWAT during aging, providing a basis for the potential regulatory effect of dWAT on aging HFs.

Platelet-rich plasma for androgenic alopecia: A randomized, placebo-controlled, double-blind study and combined mice model experiment.

BACKGROUND: Platelet rich plasma (PRP) has been accepted as a potential therapy for treating androgenetic alopecia (AGA). OBJECTIVE: To fully clarify the underling molecular mechanisms of PRP action on hair growth and promote its clinical applications. METHODS: In this study, we used mice models and protein biochip to explore the specific mechanisms of PRP regulating hair growth. Then, we performed a randomized, placebo-controlled, double-blind, half-head study of 52 AGA patients to verify the therapeutic efficacy of PRP in Chinese AGA patients. RESULTS: The results confirmed that PRP treatment boosted hair regrowth, accelerated hair cycling, and the effect sustained for more than one hair cycle in mice. Protein biochip evaluation confirmed remarkably upregulated ß-Catenin, PDGF, and AKT signaling and repressed p53 signaling in PRP injection group. Clinically, mean hair count, density, diameter, and anagen hair ratio in PRP group showed a significant improvement at 6 month comparing to control side. CONCLUSIONS: Overall, we elucidated the specific molecular mechanism of PRP action on hair growth and proved the therapeutic efficacy and safety of PRP in Chinese AGA patients.

Large-Scale Beard Extraction Enhances the Cosmetic Results of Scalp Hair Restoration in Advanced Androgenetic Alopecia in East Asian Men: A Retrospective Study.

INTRODUCTION: Beard hair serves as an important additional donor supply to support hair transplantation in hirsute patients with extensive alopecia and lacking sufficient occipital hair. However, the efficacy and safety of large-scale beard hair extraction have not been studied extensively in the East Asian population. METHODS: Data obtained from hirsute patients with extensive alopecia who underwent hair transplantation between March 2017 and December 2018 at Nanfang Hospital were analyzed. Occipital and beard hair were evaluated separately during the pre-, intra-, and post-operative periods. Individual beard hair follicular units (FUs) were harvested under tumescence using a hollow punch with an outer diameter of 0.8-0.9 mm. Follow-up examinations were scheduled at 3-5 days, 1 month, and 9 months postoperatively to check for complications, determine the survival rate of mixed, transplanted FU grafts, and assess patient satisfaction. Data were collected and analyzed statistically. RESULTS: A total of 36 hirsute, male patients with advanced androgenetic alopecia (AGA) (Norwood-Hamilton V-VI) were included in this study. The density of the occipital and beard areas was 78.6 ± 4.6 and 48.4 ± 9.3 FU, respectively. It took 3.1 ± 0.9 h to harvest 3135 ± 863 FUs from the occipital area and 2.1 ± 0.6 h to harvest 2352 ± 599 FUs from the beard area. The transection rate for occipital FUs and beard FUs was 3.7 ± 0.4 and 3.9 ± 0.2%, respectively. Completion of the operation took approximately 10.0 ± 0.9 h, and no serious complications were reported 5 days after the procedure. An FU survival rate of 95.7 ± 1.6% was observed at 9 months after transplantation, with no visible hypopigmented scars observed in the bare areas. All patients were satisfied with the resulting cosmetic appearance. CONCLUSION: Large-scale beard extraction, when combined with occipital hair extraction, is a safe and effective treatment to enhance the cosmetic appearance of East Asian men with advanced AGA.

Efficacy of Platelet-rich Plasma for Treating Androgenic Alopecia of Varying Grades.

BACKGROUND AND OBJECTIVES: Platelet-rich plasma (PRP) has received growing attention as a valuable therapeutic tool in androgenetic alopecia (AGA). However, knowledge regarding specific effectiveness and satisfaction of PRP for different grades of AGA in male pattern hair loss (MPHL) and female pattern hair loss (FPHL) is missing. This study aims to ascertain and compare the efficacy and safety of PRP treatment for different grades of AGA in males and females over 6 months. METHODS: In this study, 51 MPHL patients with Norwood-Hamilton stage II-V and 42 FPHL patients with Ludwig stage I to III were enrolled for 6 monthly sessions of PRP injections. A longitudinal analysis was used to compare the hair density, thickness, and hair pull test over 6 months for MPHL and FPHL through generalized estimating equation (GEE) models. Phototrichograms of scalp inflammation and oil secretion, global photographs and overall patient satisfaction were also assessed. RESULTS: Consequently, improvement of hair density, hair thickness, hair pull test, the level of scalp inflammation and oil secretion were observed with statistical significance in all stages for both MPHL and FPHL at 6 months. Noteworthy, lower level of alopecia (Grade II, III in MPHL and Grade I in FPHL) had better response to PRP, and also had a better tendency of increment of hair growth than that of high-grade patients with prolonged treatment. CONCLUSIONS: PRP injections, as an efficacious and reliable therapy, can be recommended for Grade II and Grade III in MPHL and Grade I in FPHL.

Fecal Microbiota Transplantation for Ulcerative Colitis: A Systematic Review and Meta-Analysis.

BACKGROUND: Fecal microbiota transplantation (FMT) has been recognized as a novel treatment for ulcerative colitis (UC). However, its efficacy and safety remain unclear. OBJECTIVE: We conducted this systematic review to assess the efficacy and safety of FMT in UC. DATA SOURCES: PubMed, EMBASE, Cochrane Central, Web of Science Core Collection, and three other Chinese databases were searched for reports of FMT in UC with clear outcomes. DATA EXTRACTION AND SYNTHESIS: We estimated pooled rates [with 95% confidence interval (CI)] of clinical remission among 15 cohort studies and clinical response among 16 cohort studies. RESULTS: Twenty five studies (2 randomized controlled trials, 15 cohort studies, and 8 case studies) with 234 UC patients were included. Overall, 41.58% (84/202) patients achieved clinical remission (CR) and 65.28% (126/193) achieved clinical response. Among the cohort studies, the pooled estimate of patients who achieved CR and clinical response were 40.5% (95% CI 24.7%-58.7%), and 66.1% (95% CI 43.7%-83.0%). Most adverse events were slight and self-resolving. The analyses of gut microbiota in 7 studies showed that FMT could increase microbiota diversity and richness, similarity, and certain change of bacterial composition. CONCLUSION: FMT provides a promising effect for UC with few adverse events. Successful FMT may be associated with an increase in microbiota diversity and richness, similarity, and certain change of bacterial composition.